Recent investigations, e.g., Gordon, Huxley and Julian, J. Physiol. 184, 170, 1966; Julian, J. Physiol., 218, 117, 1971; and Julian and Sollins, Circ. Res., 37, 299, 1975, have begun to correlate the contractile performances of heart and skeletal muscles to their basic microscopic and molecular structure and biochemical functioning. My objective is to continue these kinds of investigations with the goal of discovering the basic laws governing muscle contractions. Muscle force, length, speed of shortening and stiffness will be related to the length of the sarcomere, the fundamental unit of striated muscle, and to the level of activation, set by the fraction of myofibrillar regulating sites filled with calcium. The work proposed here will focus on the effects that partial activation may have on force development, speed of shortening, and stiffness. Since there is good evidence indicating that partial activation is the state existing physiologically, the results should provide new information about the general applicability of the sliding filament, cross-bridge model to striated muscle contraction. In addition, muscle obtained from hearts that have undergone hypertrophy will be compared to normal heart muscle to determine whether a characteristic abnormality in contractile performance exists in hypertrophied muscle. Most heart muscle physiologists have assumed that the early ideas of how skeletal muscles work could be directly applied to heart muscle studies. Since many of these ideas no longer apply to skeletal muscle, it is likely that new studies of heart muscle contraction based on modern views of how skeletal muscles work will lead to a deeper understanding of the factors regulating both normal and diseased heart muscle performance. This will make it possible to better understand the basis for heart failure in which the heart usually becomes hypertrophied and is no longer able to pump an adequate supply of blood. This in turn should lead to the development of ways to either prevent or ameliorate heart failure.